A study of human and primate oral epitheluim in vitro is proposed. Two basic culture techniques, primary cell outgrowth and primary cell suspensions, will be studied using varying conditions, temperature and sera. Once optimal conditions are selected for the short term culture of human and primate oral epithelium, cells will be cultured on a variety of carefully defined connective tissue substrata including types I and III collagen gels, collagen-proteoglycan gels and an in vitro formed basal lamina (Descemet's membrane). The collagens will be extracted and purified under conditions designed to maintain the integrity of the native molecule. Collagen gels will be formed under physiologic conditions of pH, ionic strength and temperature. The interaction of epithelial cells with the various substrata will be assessed in a variety of ways (cell aggregation, migration and growth characteristics) in addition to a detailed phase microscopic - ultrastructural study of the cell - substratum interface. These studies will be under taken to determine whether epithelial cells grown in culture on defined "physiological" substrata will interact with them in fashions which are similar to epithelial-connective tissue interactions observed in vivo. Principle methodologies to be employed include: cell culture, phase and electron microscopy, a variety of extraction techniques and gel electrophoresis. This study anticipates defining sets of in vitro conditions which will permit the study of well differentiated oral epithelial cell responses to bacterial or viral products, immunoglobulins, antimetabolites or carcinogens.